The present invention relates to protocols for nuclear imaging, and more particularly, to protocols for nuclear imaging, without coincidence, with sensitivity which meets, and even outperforms that of PET, in terms of speed and spatial resolution, and with a high spectral resolution not available in PET.
Radionuclide imaging aims at obtaining an image of a radioactively labeled substance, that is, a radiopharmaceutical, within the body, following administration, generally, by injection. The substance is chosen so as to be picked up by active pathologies to a different extent from the amount picked up by the surrounding, healthy tissue; in consequence, the pathologies are operative as radioactive-emission sources and may be detected by radioactive-emission imaging. A pathology may appear as a concentrated source of high radiation, that is, a hot region, as may be associated with a tumor, or as a region of low-level radiation, which is nonetheless above the background level, as may be associated with carcinoma.
A reversed situation is similarly possible. Dead tissue has practically no pick-up of radiopharmaceuticals, and is thus operative as a cold region.
The mechanism of localization of a radiopharmaceutical in a particular organ of interest depends on various processes in that particular organ such as antigen-antibody reactions, physical trapping of particles, receptor site binding, removal of intentionally damaged cells from circulation, and transport of a chemical species across a cell membrane and into the cell by a normally operative metabolic process. A summary of the mechanisms of localization by radiopharmaceuticals is found in http://www.lunis.luc.edu/nucmed/tutorial/radpharm/i.htm.
The particular choice of a radionuclide for labeling antibodies depends upon the chemistry of the labeling procedure and the isotope nuclear properties, such as the number of gamma rays emitted, their respective energies, the emission of other particles such as beta or positrons, the isotope half-life, and the decay scheme.
In PET imaging, positron emitting radio-isotopes are used for labeling, and the imaging camera detects coincidence photons, the gamma pair of 0.511 Mev, traveling in opposite directions. Each coincident detection defines a line of sight, along which annihilation takes place. As such, PET imaging collects emission events, which occurred in an imaginary tubular section enclosed by the PET detectors. A gold standard for PET imaging is PET NH3 rest myocardial perfusion imaging with N-13-ammonia (NH3), at a dose level of 740 MBq, with attenuation correction. Yet, since the annihilation gamma is of 0.511 Mev, regardless of the radio-isotope, PET imaging does not provide spectral information, and does not differentiate between radioisotopes.
In SPECT imaging, primarily gamma emitting radio-isotopes are used for labeling, and the imaging camera is designed to detect the actual gamma emission, generally, in an energy range of approximately 11-511 KeV. Generally, each detecting unit, which represents a single image pixel, has a collimator that defines the solid angle from which radioactive emission events may be detected.
Because PET imaging collects emission events, in the imaginary tubular section enclosed by the PET detectors, while SPECT imaging is limited to the solid collection angles defined by the collimators, generally, PET imaging has a higher sensitivity and spatial resolution than does SPECT. Therefore, the gold standard for spatial and time resolutions in nuclear imaging is defined for PET.
Although radiopharmaceuticals are powerful labeling tools, their recommended maximum dose must be taken into account when using these agents for imaging. In order to minimize exposure to the tissue, radiopharmaceuticals, which have a long half life, and radiopharmaceuticals, which have radioactive daughters, are generally avoided.
The recommended maximum doses of radiopharmaceuticals are 5 rems for a whole body dose and 15 rads per organ, while the allowable dose for children is one tenth of the adult level. The per-organ criterion protects organs where accumulation takes place. For example, radiopharmaceuticals for which removal is primarily by the liver should be administered at a lower dose than those for which removal is partly by the liver and partly by the kidney, because in the former, a single organ is involved with the removal, and in the latter, there is sharing of the removal.
Radiopharmaceutical behavior in vivo is a dynamic process. Some tissues absorb radiopharmaceuticals faster than others or preferentially to others, and some tissues flush out the radiopharmaceuticals faster than others or preferentially to others, so the relative darkness of a given tissue is related to a time factor. Since the uptake clearance of such a radiopharmaceutical by the various tissues (target and background) varies over time, standard diagnosis protocols usually recommend taking an image at the time at which the ratio of target emission versus background emission is the highest.
Yet, this approach produces a single parameter per voxel of the reconstructed image, a level of gray, at a specific time, and ignores the information that could be obtained from the behavior of a radiopharmaceutical as a function of time.
Dynamic imaging, on the other hand, attempts to acquire the behavior of a radiopharmaceutical as a function of time, for example, to measure perfusion in myocardial tissue. Dynamic imaging is advantageous to static imaging, as it provides a better measure of blood flow, it is more sensitive to ischemia than static imaging, and both perfusion as absolute blood flow and coronary flow reserve as well as myocardial viability may be obtained from a single imaging session.
It is possible to design highly sensitive SPECT imaging cameras with the sensitivity and resolution of PET imaging cameras. For example, PCT IL2006/000059 assigned to Spectrum Dynamics LLC., discloses a highly sensitive radioactive-emission camera, which opens a new realm in SPECT-type imaging. Unlike other SPECT imaging cameras, this camera is viable for dynamic studies. Accordingly, it may be used to compare the rates of change of radiopharmaceutical in a tissue with spectral resolution. Other SPECT imaging cameras are only capable of measuring the total concentration of a radiopharmaceutical in a tissue. As mentioned above, this is particularly important for measuring cardiac functions such as cardiac ejection parameters.
The camera disclosed in PCT IL2006/000059 is capable of faster and lower dose imaging compared to other SPECT cameras. The higher sensitivity of this camera also allows for use of new agents which in existing systems would not produce sufficient radioactivity.
The camera is also able to make use of radiopharmaceutical cocktails and dynamic imaging of multiple isotopes. Thus, dual and multiple isotope studies may be performed using spectral resolution. This may be particularly relevant for tumor diagnosis, since in some cases the difference between tumor and healthy tissue is that one picks up two agents whilst the other picks up only one of the agents as well as different radiopharmaceutical kinetics between tumor and healthy tissue.
There is an urgent need for and it would be particularly advantageous to have novel protocols with clear guidelines that may be used for nuclear imaging with SPECT cameras of high sensitivity and resolution.